title: Global clinical response in Cushing's syndrome patients treated with mifepristone.
abstract: OBJECTIVE
  Mifepristone, a glucocorticoid receptor antagonist, improves clinical status in patients with Cushing's syndrome (CS). We examined the pattern, reliability and correlates of global clinical response (GCR) assessments during a 6-month clinical trial of mifepristone in CS.
  
  
  METHODS
  Post hoc analysis of secondary end-point data from a 24-week multicentre, open-label trial of mifepristone (300-1200 mg daily) in CS. Intraclass correlation coefficient (ICC) was used to examine rater concordance, and drivers of clinical improvement were determined by multivariate regression analysis.
  
  
  METHODS
  Forty-six adult patients with refractory CS along with diabetes mellitus type 2 or impaired glucose tolerance, and/or a diagnosis of hypertension.
  
  
  METHODS
  Global clinical assessment made by three independent reviewers using a three-point ordinal scale (+1 = improvement; 0 = no change; -1 = worsening) based on eight broad clinical categories including glucose control, lipids, blood pressure, body composition, clinical appearance, strength, psychiatric/cognitive symptoms and quality of life at Weeks 6, 10, 16, and 24.
  
  
  RESULTS
  Positive GCR increased progressively over time with 88% of patients having improved at Week 24 (P < 0·001). The full concordance among reviewers occurred in 76·6% of evaluations resulting in an ICC of 0·652 (P < 0·001). Changes in body weight (P < 0·0001), diastolic blood pressure (P < 0·0001), two-hour postoral glucose challenge glucose concentration (P = 0·0003), and Cushingoid appearance (P = 0·022) were strong correlates of GCR.
  
  
  CONCLUSIONS
  Mifepristone treatment for CS results in progressive clinical improvement. Overall agreement among clinical reviewers was substantial and determinants of positive GCR included change in weight, blood pressure, glucose levels and appearance.
authors.affiliation: Medicine and Neurosurgery, Stanford University, Stanford, CA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Katznelson
authors.forename: D Lynn
authors.initials: DL
authors.lastname: Loriaux
authors.forename: David
authors.initials: D
authors.lastname: Feldman
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Braunstein
authors.forename: David E
authors.initials: DE
authors.lastname: Schteingart
authors.forename: Coleman
authors.initials: C
authors.lastname: Gross
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy; D006727:Hormone Antagonists / Q000008:administration & dosage; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage*; D011788:Quality of Life; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone